Oxidative autoaggression by phagocytes in human peritonitis.
In 60 abdominal exudates from patients with the diagnosis of either acute or persistent (chronic) peritonitis, indicators of phagocyte-derived oxidative systems (myeloperoxidase, chemiluminescence) and proteases (elastase) were measured. These exudates reveal a picture of maximal inflammatory activation. Both types of exudates (30 each) showed a significant influx of inflammatory cells, with the mean leucocyte count being 73,000 microL and 32,000 microL-1 respectively. Local myeloperoxidase concentrations were approximately 1000-fold greater than that of normal plasma. Spontaneous and elicitable chemiluminescence--indicators of phagocyte respiratory burst activity--were dramatically increased. In addition, levels of extracellularly released elastase (from neutrophils) were found to be up to about 1000-fold that of normal plasma values. Although most of the elastase detected in the exudates was complexed with alpha 1-proteinase inhibitor (alpha 1 PI), enzymatically active elastase could be measured in approximately 60% of the samples being investigated. As there was an excess of immunoreactive alpha 1 PI in these exudates, the free elastase activity implies that much of the alpha 1 PI was inactive, presumably subjected to oxidative destruction. Moreover, a trypsin-inhibitory activity to antigen ratio below 1 (mean = 0.81) in 75% of the purulent exudates indicated also partial proteolytic degradation of alpha 1 PI. In contrast, 16 clear exudates (no bacteria, white cell count below 500 microL-1) taken from the non-infected peritoneal cavity of patients undergoing intra-abdominal surgery revealed a similar permeability increase of the peritoneum but did not show relevant oxidative and proteolytic activity or destruction of alpha 1 PI compared with purulent specimens. Thus, only the inflammatory process of peritonitis appears to result in an overwhelming local phagocytic activity that initiates and maintains protease inhibitor consumption and/or inactivation. The tremendous oxidative potential found in purulent exudates may cause destruction in a wide variety of defence systems.
Billing
A G
AG
Chirurgische Klinik, Universität München, Klinikum Grosshadern, Munich, Germany.
Jochum
M
M
Fröhlich
D
D
Cheronis
J C
JC
Fritz
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D006868:Hydrolysis; D019272:Leukocyte Elastase / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D010447:Peptide Hydrolases / Q000378:metabolism; D010538:Peritonitis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010586:Phagocytes / Q000201:enzymology / Q000378:metabolism*; D016897:Respiratory Burst; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D016877:Oxidants; D000515:alpha 1-Antitrypsin; C037741:alpha 1-antitrypsin-leukocyte elastase complex; D010447:Peptide Hydrolases; D019272:Leukocyte Elastase